The mechanisms by which mammalian cells regulate their proliferative capacity are not known but events occurring in the G1 phase of the cell cycle are thought to be of major importance. In order to facilitate the study of cell-cycle events important to cell growth control, we have cloned mouse DNA segments containing sequences whose expression is induced by mitogenic stimulation of cultured mouse embryo cells by epidermal growth factor (EGF). Studies conducted during the past year have shown that beta-\and gamma-cytoskeletal actin genes are included in the domain of specific EGF-regulated sequences. The enhanced transcription of these genes is detectable within minutes of EGF binding but is transitory and returns to basal levels within an hour. However, an inhibitor of protein synthesis, cycloheximide, was found to greatly increase both the magnitude and the duration of EGF-induced actin gene transcription. This effect is specific in that neither alpha-tubulin nor alpha-skeletal muscle actin genes are stimulated by either EGF or cycloheximide. These data demonstrate a relationship between an important set of cytoskeletal protein genes and the response of cells to growth factors. Furthermore, these data suggest the involvement of a specific repressor of transcription in the EGF-dependent regulation of these genes. This research now seeks to test several predictions which arise from this hypothesis including the requirement for specific DNA regulatory sequences. Knowledge of the molecular mechanisms underlying the regulation of specific gene expression by peptide growth factors will broaden our understanding of cellular growth control and may ultimately contribute to a better understanding of factors leading to both cell transformation and cell senescence. (G)